Glucose Metabolism of Hippocampal Subfields in Medial Temporal Lobe Epilepsy.

PURPOSE: Reduced glucose metabolism in the hippocampus is commonly observed in cases of medial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS). Glucose metabolism among the various hippocampal subfields has not been thoroughly investigated. PATIENTS AND METHODS: This study examined 29 patients (18 females; 15-58 years) diagnosed with HS who underwent surgery for drug-resistant epilepsy. FreeSurfer 7.1.1 was used in the processing of MRI data and 18 F-FDG PET scans to derive volumetric data and the FDG SUVr in the whole hippocampus and hippocampal subfields, including the CA1, CA2-4, granule cell and molecular layer of the dentate gyrus (GC-ML-DG), and subiculum. Asymmetries in the volume and SUVr between the 2 sides from the subfields of the hippocampus were defined in terms of an asymmetry index. Comparisons of the asymmetry index among these regions were performed. The correlations between asymmetry index values and postoperative outcomes and presurgical neuropsychological test results were also evaluated. RESULT: The CA1, CA2-4, subiculum, GC-ML-DG, and whole hippocampus presented reductions in volume and hypometabolism ipsilateral to MTLE. Asymmetries in volume and SUVr were significantly less pronounced in the CA1 and subiculum than in the CA2-4 or GC-ML-DG. Postoperative seizure outcomes were not correlated with the asymmetry index for volume or SUVr in any hippocampal subfield. In cases of left MTLE, scores of immediate logical memory and delayed logical memory were positively correlated with the asymmetry index for SUVr in the following subfields: CA1 ( R = 0.829, P = 0.021; R = 0.770, P = 0.043), CA2-4 ( R = 0.825, P = 0.022; R = 0.894, P = 0.007), subiculum ( R = 0.882, P = 0.009; R = 0.853, P = 0.015), GC-ML-DG ( R = 0.850, P = 0.015; R = 0.796, P = 0.032), and whole hippocampus ( R = 0.841, P = 0.018; R = 0.822, P = 0.023). In cases of right MTLE, the scores for delayed face memory were positively correlated with the asymmetry index for SUVr in the subiculum ( R = 0.935, P = 0.006). CONCLUSIONS: In cases of HS, changes in glucose metabolism levels varied among the hippocampal subfields. Asymmetries in glucose metabolism among the CA-1, CA2-4, subiculum, and GC-ML-DG subregions were correlated with scores for verbal memory among patients with left MTLE. Asymmetric glucose metabolism in the subiculum was also correlated with visual memory scores among patients with right MTLE.

Cross-task specificity and within-task invariance of cognitive control processes.

Cognitive control involves flexibly combining multiple sensory inputs with task-dependent goals during decision making. Several tasks involving conflicting sensory inputs and motor outputs have been proposed to examine cognitive control, including the Stroop, Flanker, and multi-source interference task. Because these tasks have been studied independently, it remains unclear whether the neural signatures of cognitive control reflect abstract control mechanisms or specific combinations of sensory and behavioral aspects of each task. To address these questions, we record invasive neurophysiological signals from 16 patients with pharmacologically intractable epilepsy and compare neural responses within and between tasks. Neural signals differ between incongruent and congruent conditions, showing strong modulation by conflicting task demands. These neural signals are mostly specific to each task, generalizing within a task but not across tasks. These results highlight the complex interplay between sensory inputs, motor outputs, and task demands underlying cognitive control processes.

Strategic infarct location for post-stroke seizure.

Post-stroke seizure (PSS) can have a strong negative impact on functional recovery after stroke. Researchers have identified numerous risk factors of PSS; however, the relationship between infarction location and PSS remains unclear. We recruited patients who presented with an acute cerebral infarction between 2012 and 2017 and suffered from seizures within 1 year after stroke (PSS group). PSS group was subgrouped into early-PSS and late-PSS groups based on the interval between seizure and stroke. We also recruited an equal number of acute cerebral infarction patients without post-stroke seizures during the follow-up period (Non-PSS group). All brain MRIs from the two groups were processed, whereupon normalized infarct maps from the PSS and Non-PSS groups were compared via voxel- and volumetric-based analyses. A total of 132 subjects were enrolled in the study, including PSS (n = 66, consisting of 31 early-PSS and 35 late-PSS) and Non-PSS (n = 66) patients. No significant differences were observed between the two groups in terms of stroke lateralization or severity. Image analysis revealed that the volume of infarction was larger in the PSS group than in the Non-PSS group; however, the difference did not reach the level of significance. Unlike the Non-PSS group, the PSS group presented hot spots over the left central region, left superior parietal lobule, and right frontal operculum. We observed differences between the distribution of hot spots among patients with early-PSS and those with late-PSS. We found that some brain regions were significantly associated with the development of PSS after ischemic stroke, and these regions differed between cases of early and late PSS. It appears that the location of infarction could help clinicians assess the risk of PSS in specific post-stroke stages.

Reliability and validity of the traditional Chinese version of the GAD-7 in Taiwanese patients with epilepsy.

BACKGROUND: Generalized anxiety disorder (GAD) is the second most common psychiatric comorbidity of epilepsy. GAD has a negative impact on seizure control, and it is underrecognized. The Generalized Anxiety Disorder 7-item (GAD-7) questionnaire is useful for screening GAD in patients with epilepsy (PWE). This study aimed to validate the traditional Chinese version of the GAD-7 for Taiwanese patients by obtaining data on adult PWE from our hospital. METHOD: PWE were recruited from the Taipei Veterans General Hospital from April 2017 to January 2020. The mood disorder module of the Mini International Neuropsychiatric Interview (MINI) was used for the psychiatric assessment. The traditional Chinese version of the GAD-7 and the Beck Anxiety Inventory were included as self-rated psychiatric evaluation. To investigate the psychometric properties, internal consistency, external validation, and receiver operator characteristic (ROC) curve analysis were conducted to assess the utility of the Taiwanese version of the GAD-7. RESULTS: We recruited 109 patients in the present study. Seventeen patients (15.9%) had GAD according to the MINI. The mean GAD-7 score was 10.28 ± 10.68. All the GAD-7 items were significantly and positively associated with the corrected overall GAD-7 score (Cronbach's alpha = 0.928, p < 0.0001). The cut-off point for the GAD-7 in ROC curve analysis was 7. The patients with GAD were more likely to be female and single. CONCLUSION: The traditional Chinese version of the GAD-7 is a reliable and valid self-report questionnaire for detecting GAD in Taiwanese PWE.

Clinical characteristics and long-term outcome of cerebral cavernous malformations-related epilepsy.

OBJECTIVE: Cerebral cavernous malformations (CCMs) present variably, and epileptic seizures are the most common symptom. The factors contributing to cavernoma-related epilepsy (CRE) and drug resistance remain inconclusive. The outcomes of CRE after different treatment modalities have not yet been fully addressed. This study aimed to characterize the clinical features of patients with CRE and the long-term seizure outcomes of medical and surgical treatment strategies. METHODS: This was a retrospective cohort of 135 patients with CCM who were diagnosed in 2007-2011 and followed up for 93.6 months on average. The patients were divided into drug-resistant epilepsy (DRE; n = 29), non-DRE (n = 45), and no epilepsy (NE; n = 61). RESULTS: Temporal CCM was the factor most strongly associated with the development of both CRE and DRE. The majority of patients with single temporal CCMs had CRE (86.8%, n = 33), and 50% had DRE, whereas only 14.7% (n = 5) with a nontemporal supratentorial CCM had DRE (p < .05). The most common lesion site in the DRE group was the mesiotemporal lobe (50%). Multiple CCMs were more frequently observed in the CRE (29.2%) than the NE (11.5%) group (p < .05). In patients with CRE, multiple lesions were associated with a higher rebleeding rate (odds ratio = 11.1), particularly in those with DRE (odds ratio = 15.4). The majority of patients who underwent resective surgery for DRE (76.5%, n = 13) achieved International League Against Epilepsy Class I and II seizure outcomes even after a long disease course. SIGNIFICANCE: Temporal CCM not only predisposes to CRE but also is a major risk factor for drug resistance. The mesiotemporal lobe is the most epileptogenic zone. Multiple CCMs are another risk factor for CRE and increase the rebleeding risk in these patients. Surgical resection could provide beneficial long-term seizure outcomes in patients with DRE.

Machine Learning Quantitative Analysis of FDG PET Images of Medial Temporal Lobe Epilepsy Patients.

PURPOSE: 18F-FDG PET is widely used in epilepsy surgery. We established a robust quantitative algorithm for the lateralization of epileptogenic foci and examined the value of machine learning of 18F-FDG PET data in medial temporal lobe epilepsy (MTLE) patients. PATIENTS AND METHODS: We retrospectively reviewed patients who underwent surgery for MTLE. Three clinicians identified the side of MTLE epileptogenesis by visual inspection. The surgical side was set as the epileptogenic side. Two parcellation paradigms and corresponding atlases (Automated Anatomical Labeling and FreeSurfer aparc + aseg) were used to extract the normalized PET uptake of the regions of interest (ROIs). The lateralization index of the MTLE-associated regions in either hemisphere was calculated. The lateralization indices of each ROI were subjected for machine learning to establish the model for classifying the side of MTLE epileptogenesis. RESULT: Ninety-three patients were enrolled for training and validation, and another 11 patients were used for testing. The hit rate of lateralization by visual analysis was 75.3%. Among the 23 patients whose MTLE side of epileptogenesis was incorrectly determined or for whom no conclusion was reached by visual analysis, the Automated Anatomical Labeling and aparc + aseg parcellated the associated ROIs on the correctly lateralized MTLE side in 100.0% and 82.6%. In the testing set, lateralization accuracy was 100% in the 2 paradigms. CONCLUSIONS: Visual analysis of 18F-FDG PET to lateralize MTLE epileptogenesis showed a lower hit rate compared with machine-assisted interpretation. While reviewing 18F-FDG PET images of MTLE patients, considering the regions associated with MTLE resulted in better performance than limiting analysis to hippocampal regions.

Acute withdrawal of new-generation antiepileptic drugs in epilepsy monitoring units: Safety and efficacy.

INTRODUCTION: Acute withdrawal of antiepileptic drugs (AEDs) is a safe and effective approach to provoking seizures in order to complete video-electroencephalogram (V-EEG) studies in a timely manner. Previous studies have focused only on withdrawal from conventional AEDs, and the effects of withdrawal from new-generation AEDs have not been extensively studied. MATERIALS AND METHODS: This study examined adult patients with drug-resistant epilepsy admitted to an epilepsy monitoring unit between 2015 and 2018. Patients were classified according to whether they received conventional AEDs (Con; n = 13) or new-generation AEDs (N-Gen; n = 26). We then compared the effects of withdrawing these two types of AEDs over a period of one week in terms of efficacy (time to complete V-EEG monitoring) and safety, including the incidence of cluster seizures (CS), focal to bilateral tonic-clonic seizures (FBTCS) and status epilepticus (SE). RESULTS: In both groups, approximately one week was required to complete V-EEG analysis: N-Gen group (5.6 days) and Con group (6.3 days). No differences were observed between the two groups in terms of the median number of seizures, the onset of the 1st seizure, the distribution of CS, FBTCS, or SE. Following acute withdrawal of medication, a high percentage of patients with a history of CS or FBTCS, respectively, presented CS or FBTCS. CONCLUSIONS: We did not observe significant differences between patients taking new-generation AEDs and those taking conventional AEDs following withdrawal during V-EEG recording. In the current study, we employed a standard protocol for the rapid withdrawal of AEDs (daily dose reduction of 50%), which was sufficient for 80% of patients to complete V-EEG monitoring within one week.

Reliability and validity of the Taiwanese version of the Neurological Disorders Depression Inventory for Epilepsy (Tw-NDDI-E).

INTRODUCTION: Depression is the most commonly seen psychiatric co-morbidity of epilepsy. Depression in patients with epilepsy (PWE) is underrecognized. The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a useful tool to screen for major depressive episodes (MDEs) in PWE. This study validated the Taiwanese version of the NDDI-E using data from adult PWE in our hospital. METHOD: PWE were recruited from the Taipei Veterans General Hospital from April 2017 to December 2019. The Chinese version of the NDDI-E for the Taiwanese population and the Beck Depression Inventory-II (BDI-II) were completed as part of the self-rated psychiatric assessments. The mood disorder module of the Mini International Neuropsychiatric Interview (MINI) was completed as part of the psychiatric assessment before the self-rated assessment. Internal consistency, external validation, and receiver operator characteristic (ROC) curve analysis were used to assess the utility of the Taiwanese version of the NDDI-E. RESULTS: We recruited 109 patients during the 33-month study period. The mean age was 33.1 ± 8.94 years old. The mean NDDI-E score was 12.32 ± 4.96. The mean BDI-II score was 13.26 ± 12.77. All NDDI-E items were significantly positively associated with the corrected overall NDDI-E score (Cronbach's alpha = 0.902, r = 0.825, p < 0.0001). The cut-off point for the NDDI-E determined with receiver operating characteristic (ROC) curve analysis is 15 (sensitivity = 85.0%, specificity = 87.64%). CONCLUSION: The Chinese version of the NDDI-E adapted for the Taiwanese population is a reliable and valid self-reported questionnaire for detecting MDE in Taiwanese PWE.

Influence of Climate on the Incidence of RCVS - A Retrospective Study From Taiwan.

BACKGROUND: Cold weather is reportedly a precipitator of reversible cerebral vasoconstriction syndrome (RCVS) in a few cases. We systematically investigated whether meteorological factors correlate with the occurrence of RCVS. METHODS: We conducted a retrospective analysis of a cohort of patients diagnosed with RCVS or probable RCVS, based on International Classification of Headache Disorders, third edition (ICHD-3) criteria, in a hospital-based headache center from March 2005 to February 2014. Monthly averages of local weather data measured in Taipei were obtained from the Central Weather Bureau in Taiwan. Primary weather variables were compared with the number of monthly new-onset cases of RCVS. RESULTS: We recruited 226 patients with established RCVS and 72 patients with probable RCVS during a 108-month study period. Incidence of RCVS was higher in winter than summer months (3.3 persons/month [SD: 2.0] vs 2.1 persons/month [SD: 1.5], P = .013). The monthly incidence of RCVS correlated negatively with mean daily temperature (r = -0.231, P = .016) and average precipitation (r = -0.269, P = .005), but positively with barometric pressure (r = 0.274, P = .004). These 3 correlated meteorological factors together explained about 10% of the variance in RCVS monthly incidence (R2  = 0.095, P = .015). CONCLUSION: RCVS was found to be more common in winter months and to be associated with weather variables in Taiwan. Further studies are needed to explore the underlying mechanisms of these associations.

Role of AMP-activated protein kinase in α-lipoic acid-induced vasodilatation in spontaneously hypertensive rats.

BACKGROUND: Adenosine monophosphate (AMP)-activated protein kinase (AMPK) has recently emerged as an attractive and novel target for the regulation of vascular smooth muscle contraction. The present study investigated the vasodilatory effects of α-lipoic acid (α-LA) and the possible mechanism of its action on aortic rings from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). METHODS: Aortae were removed from WKY and SHR, and contractile responses to acetylcholine and α-LA studied in organ chamber. Phosphorylated AMPK (pAMPK), phosphorylated Peutz-Jeghers syndrome kinase LKB1 (pLKB1) and calcium/calmodulin-dependent protein kinase (CaMKK) protein level were measured in SHR, WKY, and aortic smooth muscle (A10) cells. RESULTS: α-LA (1-500 µmol/l) produced a concentration-dependent relaxation of precontracted aortic rings from 8- and 16-week-old SHR, but not in those from WKY rats. This vasodilatory effect of α-LA did not change after preincubation with N(G)-nitro-L-arginine methyl ester (100 µmol/l), but significantly suppressed by an AMPK inhibitor, compound C (40 µmol/l). The expression of pAMPKα, pLKB1, and CaMKK were also significantly reduced in endothelium-denuded arteries from 16-week-old SHR compared with those from younger SHR or age-matched WKY rats. After incubation with α-LA (100 µmol/l), the expression of pAMPKα and pLKB1 was significantly increased in the endothelium-denuded aortas from 16-week-old SHR, the expression of CaMKK was more reduced in the endothelium-denuded aortas of 8-week-old SHR, but this was not observed in WKY rats. α-LA also activated AMPKα phosphorylation in A10 cells. CONCLUSIONS: The effects of α-LA on vascular relaxation in SHR result from the enhanced phosphorylation of LKB1-AMPK in aortic smooth muscle.